title: Paeonia lactiflora Pall inhibits bladder cancer growth involving phosphorylation of Chk2 in vitro and in vivo.
abstract: BACKGROUND
  Extracts of Paeonia lactiflora Pall (RPA), a traditional Chinese medicines has been shown to treat cancers.
  
  
  OBJECTIVE
  The purpose of this study is to evaluate the anticancer effect of RPA in urinary bladder carcinoma in vitro and in vivo.
  
  
  METHODS
  The cell viability was analyzed with DAPI. Flow cytometry and Western blot were used to study the apoptosis and cell cycle related mechanism. A rat model of bladder cancer was induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (OH-BBN). Tumors were analyzed with immunohistochemical analysis.
  
  
  RESULTS
  Our data suggested that RPA inhibits growth of bladder cancer via induction of apoptosis and cell cycle arrest. Treatment of TSGH-8301 cells with RPA resulted in G2-M phase arrest that was associated with a marked decline in protein levels of cdc2, cyclin B1, cell division cycle 25B (Cdc25B) and Cdc25C. We also reported that RPA-mediated growth inhibition of TSGH-8301 cells was correlated with activation of checkpoint kinase 2 (Chk2). Herein, we further evaluated urinary bladder cancer using a model of bladder cancer induced by OH-BBN. Analysis of tumors from RPA-treated rats showed significant decrease in the expression of Bcl2, cyclin D1, and PCNA, and increase in the expression of p-Chk2 (Thr-68), Bax, and Cip1/p21.
  
  
  CONCLUSIONS
  Our data provide the experimental evidence that RPA could modulate apoptosis in models of bladder cancer.
authors.affiliation: Institute of Biochemistry and Biotechnology, College of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Ting-Tsz
authors.initials: TT
authors.lastname: Ou
authors.forename: Cheng-Hsun
authors.initials: CH
authors.lastname: Wu
authors.forename: Jeng-Dong
authors.initials: JD
authors.lastname: Hsu
authors.forename: Charng-Cherng
authors.initials: CC
authors.lastname: Chyau
authors.forename: Huei-Jane
authors.initials: HJ
authors.lastname: Lee
authors.forename: Chau-Jong
authors.initials: CJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002085:Butylhydroxybutylnitrosamine; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D064447:Checkpoint Kinase 2; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D029596:Paeonia; D010766:Phosphorylation; D008517:Phytotherapy; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D019459:Urothelium
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D018797:Cell Cycle Proteins; D004365:Drugs, Chinese Herbal; D011518:Proto-Oncogene Proteins; D002085:Butylhydroxybutylnitrosamine; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; C578632:Chek2 protein, rat; D017346:Protein Serine-Threonine Kinases